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Personalized PRRT of Neuroendocrine Tumors (P-PRRT)

Primary Purpose

Neuroendocrine Tumors, Carcinoid Tumor, Carcinoma, Neuroendocrine

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
177Lu-Octreotate
Sponsored by
CHU de Quebec-Universite Laval
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring Neuroendocrine tumors, Personalized, Peptide receptor radionuclide therapy, PRRT, 177Lu-DOTATATE, 177Lu-octreotate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient suffering from a progressive and/or symptomatic NET (any site);
  • Patient ineligible to, or refusing a potentially curative treatment such as surgical resection;
  • Patient who did not respond, is intolerant or refuses other indicated and available palliative treatments;
  • Demonstration of overexpression of somatostatin receptor by tumor lesions by scintigraphic imaging (Octreoscan or 68Ga positron emission tomography.

Exclusion Criteria:

  • Pregnancy;
  • Breastfeeding;.
  • Very limited survival prognosis (i.e. less than a few weeks, because of the NET disease or any other condition) or Eastern Cooperative Oncology Group (ECOG) 4 performance status;
  • Inability to obtain informed consent of the participant.

Sites / Locations

  • CHU de Québec - Université LavalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Personalized PRRT (P-PRRT)

Arm Description

177Lu-Octreotate (LuTate) P-PRRT will be administered as follows: Renal absorbed radiation dose will be prescribed for the 4-cycle induction course (23 Gy) and for each subsequent cycle (6 Gy), with a reduction in cases of impaired renal or bone marrow function, or significant toxicity from prior cycles. The personalized activity to be administered at each cycle will be derived from renal dose per unit of injected activity that is predicted by patient characteristics or renal dose delivered during prior cycle(s). Participants responding to the induction course of P-PRRT will be eligible to receive additional consolidation and/or maintenance cycles. Participants with prior PRRT exposure outside the trial may receive less induction cycles, or only consolidation/maintenance cycle(s).

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
Primary efficacy endpoint is the objective response rate on contrast-enhanced CT (or MRI) by RECIST criteria (and secondarily by South Western Oncology Group (SWOG) criteria) at 3 months after the 4th induction cycle of P-PRRT, in comparison to pre-treatment scan (within 3 months before commencing P-PRRT).

Secondary Outcome Measures

Progression-free survival (PFS)
Progression of disease is defined as the time from first cycle to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria.
Overall survival (OS)
Symptomatic response rate
Proportion of participants with improved, stable or worsened NET-related symptoms (frequency and severity), based on participant interviews at baseline and 3 months after completion of induction course.
Quality of life response
Proportion of participants with improved, stable or worsened quality of life score by EORTC quality of life questionnaires QLQ-C30 and QLQ-GI.NET21, administered at baseline and 3 months after induction course.
Biochemical response
Proportion of participants with improved (decreased by 25% or more), stable or worsened (increased by 25% or more) Chromogranin-A serum levels performed at baseline and 3 months after induction course.
Safety determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03

Full Information

First Posted
March 10, 2016
Last Updated
May 31, 2023
Sponsor
CHU de Quebec-Universite Laval
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1. Study Identification

Unique Protocol Identification Number
NCT02754297
Brief Title
Personalized PRRT of Neuroendocrine Tumors
Acronym
P-PRRT
Official Title
Personalized Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Phase 2 Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 12, 2016 (Actual)
Primary Completion Date
April 12, 2025 (Anticipated)
Study Completion Date
April 12, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CHU de Quebec-Universite Laval

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, peptide receptor radionuclide therapy (PRRT) with 177Lu-Octreotate (LuTate) will be personalized, i.e. administered activity of LuTate will be tailored for each patient to maximize absorbed radiation dose to tumor, while limiting that to healthy organs. The purpose of this study is to: Assess the objective (radiological), symptomatic and biochemical response rates following an induction course of personalized PRRT; Assess the overall, the disease-specific, and the progression-free survival following P-PRRT; Correlate therapeutic response and survival with tumor absorbed radiation dose; Evaluate the acute, subacute and chronic adverse events following P-PRRT; Correlate toxicity (i.e. occurence and severity of adverse events) with absorbed radiation doses to organs at risk; Optimize the quantitative SPECT imaging-based dosimetry methods in a subset of 20 patients (sub-study funded by the Canadian Institutes of Health Research). This study also has a compassionate purpose, which is to provide access to PRRT to patients.
Detailed Description
A prospective, single-center, non-comparative, open phase 2 study. In this study, personalized peptide receptor radionuclide therapy (P-PRRT) with 177Lu-Octreotate (LuTate) will be administered to patients with progressive and/or symptomatic inoperable neuroendocrine tumors (NET) of any origin expressing the somatostatin receptor. The primary objective to assess the objective response rate at 3 months following a four-cycle induction course of P-PRRT will be assessed for at least the first 85 participants. This study as a compassionate aim to provide access to personalized PRRT patients at CHU de Québec - Université Laval center, and therefore this study has no pre-determined recruitment period duration or limited number of participants, and may remain open as long as necessary to fulfill this aim. The study will continue until all participants have completed a minimum follow-up of 5 years. Interim analyses will be conducted annually.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors, Carcinoid Tumor, Carcinoma, Neuroendocrine
Keywords
Neuroendocrine tumors, Personalized, Peptide receptor radionuclide therapy, PRRT, 177Lu-DOTATATE, 177Lu-octreotate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Personalized PRRT (P-PRRT)
Arm Type
Experimental
Arm Description
177Lu-Octreotate (LuTate) P-PRRT will be administered as follows: Renal absorbed radiation dose will be prescribed for the 4-cycle induction course (23 Gy) and for each subsequent cycle (6 Gy), with a reduction in cases of impaired renal or bone marrow function, or significant toxicity from prior cycles. The personalized activity to be administered at each cycle will be derived from renal dose per unit of injected activity that is predicted by patient characteristics or renal dose delivered during prior cycle(s). Participants responding to the induction course of P-PRRT will be eligible to receive additional consolidation and/or maintenance cycles. Participants with prior PRRT exposure outside the trial may receive less induction cycles, or only consolidation/maintenance cycle(s).
Intervention Type
Drug
Intervention Name(s)
177Lu-Octreotate
Other Intervention Name(s)
LuTate, 177Lu-[DOTA0,Tyr3]octreotate, 177Lu-DOTATATE
Intervention Description
The induction course will consist in 4 cycles at 8-10 weeks intervals. Concomitant amino acids will be administered for renal protection. Intra-arterial LuTate administration will be allowed in suitable cases. Dosimetry will be based on quantitative SPECT/CT imaging. In patients with hormonal symptoms, somatostatine analogues can be given between P-PRRT cycles.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Primary efficacy endpoint is the objective response rate on contrast-enhanced CT (or MRI) by RECIST criteria (and secondarily by South Western Oncology Group (SWOG) criteria) at 3 months after the 4th induction cycle of P-PRRT, in comparison to pre-treatment scan (within 3 months before commencing P-PRRT).
Time Frame
3 months after induction course
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Progression of disease is defined as the time from first cycle to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria.
Time Frame
Time from first cycle to date of disease progression or death, reported up to 5 years after accrual closure
Title
Overall survival (OS)
Time Frame
Time from first cycle to date of death, reported up to 5 years after accrual closure
Title
Symptomatic response rate
Description
Proportion of participants with improved, stable or worsened NET-related symptoms (frequency and severity), based on participant interviews at baseline and 3 months after completion of induction course.
Time Frame
3 months after induction course
Title
Quality of life response
Description
Proportion of participants with improved, stable or worsened quality of life score by EORTC quality of life questionnaires QLQ-C30 and QLQ-GI.NET21, administered at baseline and 3 months after induction course.
Time Frame
3 months after induction course
Title
Biochemical response
Description
Proportion of participants with improved (decreased by 25% or more), stable or worsened (increased by 25% or more) Chromogranin-A serum levels performed at baseline and 3 months after induction course.
Time Frame
3 months after induction course
Title
Safety determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03
Time Frame
From the first treatment cycle administration until 5 years after accrual closure or death, whichever came first
Other Pre-specified Outcome Measures:
Title
Tumor radiation dose-response relationship
Description
Correlation between cumulative absorbed radiation dose to tumor lesions and 3-month objective response rate, as defined above
Time Frame
3 months after induction course
Title
Tumor radiation dose-survival relationship
Description
Correlation between cumulative absorbed radiation dose to tumor lesions and survival endpoints above (PFS and OS)
Time Frame
At least 5 years after first cycle or until study completion, whichever came first
Title
Renal radiation dose-chronic toxicity relationship
Description
Correlation between cumulative absorbed radiation dose to kidney and variations in glomerular filtration rate from baseline, reported annually for at least 5 years after first cycle or until study completion.
Time Frame
At least 5 years after first cycle or until study completion, whichever came first
Title
Bone marrow radiation dose-chronic toxicity relationship
Description
Correlation between cumulative absorbed radiation dose to bone marrow and chronic variations of blood counts from baseline, reported annually for at least 5 years after first cycle or until study completion.
Time Frame
At least 5 years after first cycle or until study completion, whichever came first
Title
Bone marrow radiation dose-subacute toxicity relationship
Description
Correlation between per-cycle absorbed radiation dose to bone marrow and subacute variations (nadir values between 2 and 6 weeks) of blood counts from baseline, for each cycle.
Time Frame
Time of nadir blood counts values between 2 and 6 weeks after each cycle

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient suffering from a progressive and/or symptomatic NET (any site); Patient ineligible to, or refusing a potentially curative treatment such as surgical resection; Patient who did not respond, is intolerant or refuses other indicated and available palliative treatments; Demonstration of overexpression of somatostatin receptor by tumor lesions by scintigraphic imaging (Octreoscan or 68Ga positron emission tomography. Exclusion Criteria: Pregnancy; Breastfeeding;. Very limited survival prognosis (i.e. less than a few weeks, because of the NET disease or any other condition) or Eastern Cooperative Oncology Group (ECOG) 4 performance status; Inability to obtain informed consent of the participant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Mathieu Beauregard, MD,MSc,FRCPC
Phone
418-525-4444
Email
medecine.nucleaire@mail.chudequebec.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Geneviève Filion
Phone
418-525-4444
Email
medecine.nucleaire@mail.chudequebec.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Mathieu Beauregard, MD,MSc,FRCPC
Organizational Affiliation
CHU de Québec - Université Laval
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Québec - Université Laval
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Mathieu Beauregard, MD,MSc,FRCPC
Phone
418-555-4444
Email
medecine.nucleaire@mail.chudequebec.ca
First Name & Middle Initial & Last Name & Degree
François-Alexandre Buteau, MD, FRCPC

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30506283
Citation
Del Prete M, Buteau FA, Arsenault F, Saighi N, Bouchard LO, Beaulieu A, Beauregard JM. Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):728-742. doi: 10.1007/s00259-018-4209-7. Epub 2018 Nov 30.
Results Reference
derived

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Personalized PRRT of Neuroendocrine Tumors

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